1. Field of the Invention
The field of the present invention is psoralens, aminomethylation of psoralens and aminomethylpsoralen products.
2. Prior Art
Aminomethyl groups have been introduced into psoralens by condensation of the psoralen with an alpha-halomethyl ether, displacement of the halogen from the halomethyl group with potassium phthalimide and hydrolysis of the resulting N-phthalimidomethyl with hydrazine to generate the aminomethylpsoralens. This three-step process has been described in S. T. Isaacs, C. J. Shen, J. E. Hearst, and H. Rapoport, Biochem., Vol. 16, 1058 (1977), K. Kaufman, et al., J. Heterocyclic Chem., Vol. 19, 1051 (1982), U.S. Pat. Nos. 4,124,598 and 4,294,822. All of these disclosed procedures employ volatile, hydrolytically unstable, carcinogenic haloalkyl ethers whose cancer-causing propensities have been noted (Federal Register, 39, 3756 (1974)). All of these procedures require three synthetic steps with attendant losses of time and efficiency of operation; oveall conversions from psoralen to aminomethylpsoralen of 30-50% have been reported. The conventional three-step procedure is shown below: ##STR1##